Pituitary Morphology Research Articles

Female Pituitary Size in Relation to Age and Hormonal Factors

Background: It is well known that pituitary volume decreases with age; little is known about the influences of female cycle, intake of oral contraceptives, number of given births and duration of menopause on pituitary morphology. Furthermore, these contexts have never been examined with 3-tesla MRI, from which a high spatial resolution is expected. Methods: Ninety-four women from 18 to 80 years (mean 64 years) had to answer a questionnaire concerning their cycle situation, menopause, hormone intake and childbirths before receiving a 3-tesla MRI scan (Achieva, Philips, N.V.), including a T₁-weighted TSE sequence of the sella turcica. Pituitary volumes and diameters were measured with the software iplan® (BrainLAB, Feldkirchen, Germany). Results: A significant reverse correlation was found between age and pituitary volume (p < 0.0001)/cranio-caudal diameter (p = 0.02). In addition, an age-independent influence of oral contraceptives was found, indicating smaller pituitary sizes with hormone intake (p = 0.003). Cycle phase, number of given births and onset or duration of menopause had no effects on pituitary size. Conclusion: Three-tesla MRI suggests that pituitary volume not only decreases with age, it also seems to be related to long-term hormonal changes such as intake of oral contraceptives.

Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD)

Homozygous mutations in the gene encoding the pituitary transcription factor PROP1 are associated with combined pituitary hormone deficiency (CPHD) in both mice and humans with a highly variable phenotype with respect to the severity and time of initiation of pituitary hormone deficiency. We have ascertained three pedigrees with PROP1 mutations from a large cohort of patients with variable degrees of CPHD who were screened for mutations in PROP1. Affected individuals from all three pedigrees were found to harbour novel PROP1 mutations. We have identified two siblings in one family who were homozygous for an intronic mutation (c.343-11C > G) that disrupts correct splicing resulting in the loss of exon 3 from the PROP1 transcript. Two siblings from a second, unrelated family are compound heterozygotes for two point mutations in the coding region, a missense mutation (p.R125W) that leads to impaired transcriptional activation, and a deletion of a single nucleotide (c.310delC) resulting in a frameshift and nonfunctional mutant protein. Additionally, we identified a homozygous deletion of the PROP1 locus in two patients born to consanguineous parents. Mutations in PROP1 are a frequent cause of familial CPHD. We have described four novel mutations in PROP1 in 3 pedigrees, all resulting in PROP1 deficiency by different mechanisms. The phenotypic variation observed in association with PROP1 mutations both within and between families, together with the evolving nature of hormone deficiencies and sometimes changing pituitary morphology indicates a need for continual monitoring of these patients.

Facial and pituitary morphology are related in Dutch patients with GH deficiency

Classical GH deficiency (GHD) is associated with typical phenotypic features. We have analysed standardized photographs of 137 Caucasian patients with GHD, in order to examine the relations between auxological, biochemical, pituitary and facial morphometric features. We analysed pictures of 137 patients: 73 (55 Males/18 Females) with Isolated GHD and 64 (48 M/16 F) with multiple pituitary hormone deficiency (MPHD). Of each patient, standardized frontal and lateral digital pictures were taken and analysed using Adobe Photoshop 5.0. Canthal index (CI), the relative distance between the eyes, was related to pituitary morphology. Patients with an ectopic posterior pituitary (EPP) had significantly higher CI values than patients without EPP. We found CI > 39 to be a good cut-off value to select children with highest probability of having EPP. The combination of CI > 39 with the presence of hormonal deficiencies additional to GHD strongly predicted EPP: 93% of the patients with a CI > 39 and additional hormonal deficiencies had EPP, in contrast to 77% of the patients with additional hormonal deficiencies but a CI < 39, and 29% of the patients with none of these criteria (P = 0.0001). CI, measured on digital pictures, is associated with ectopia of the posterior pituitary and this might be caused by an altered midline development, affecting both the pituitary and the facial structures of GHD patients.

Hypopituitarism in the Elderly: Multifaceted Clinical and Biochemical Presentation

Hypopituitarism (HYPO) is a rare and under-investigated pathology in the elderly. to review our case records of patients > or =65 yrs with first diagnosis of anterior global hypopituitarism, in order to evaluate presentation symptoms, etiology, biochemical and hormonal pictures, pituitary morphology, and efficacy of therapy. 15 patients (65-82 yrs) were studied: in 11 (73%) HYPO was secondary to pituitary macroadenoma (non-secreting in 10 and GH-secreting in 1); in 3 it was associated to empty sella, and in 1 to pituitary hypoplasia. major presenting symptoms were visual-field defects and asthenia (40%) but also memory and/or gait impairment and nausea (30%) and depression (20%) were significantly observed. Dyslipidemia (73%), anemia (20%) and severe hyponatremia (13%) were found. After starting substitutive therapy and clinical improvement, 10 patients with macroadenoma underwent uneventful neurosurgery, which improved visual alterations but not pituitary function. Immunohistochemistry showed positivity for FSH in one patient and for GH in one patient. Six out of the eight patients with a post-surgical tumor remnant required treatment (surgery/radiotherapy/somatostatin analogue treatment in the acromegalic patient). The diagnosis of HYPO is often delayed in the elderly, since symptoms may be ascribed to aging and associated comorbidities. In our series, most of the aspecific symptoms were retrospectively addressed to HYPO since their resolution/improvement with replacement therapy. The prevalent cause of HYPO remains non-functioning pituitary macroadenomas. Hyponatremia can be a life-threatening presenting symptom. Symptoms considered apparently aspecific in the elderly should be investigated in order to possibly diagnose an important treatable disorder as HYPO.

Three Novel Missense Mutations within the LHX4 Gene Are Associated with Variable Pituitary Hormone Deficiencies

The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency. Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations. The LHX4 gene sequence was determined from patient DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins were characterized using structural predictions, pituitary gene transcription assays, and DNA binding experiments. A total of 253 patients from 245 pedigrees with GH deficiency and deficiency of at least one additional pituitary hormone was included in the study. In five patients, three types of heterozygous missense mutations in LHX4 that result in substitution of conserved amino acids were identified. One substitution is between the LIM domains (R84C); the others are in the homeodomain (L190R; A210P). The patients have GH deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant pituitary morphology. Structural models predict that the aberrant L190R and A210P LHX4 proteins would have impaired DNA binding and gene activation properties. Consistent with these models, EMSAs and transfection experiments using pituitary gene promoters demonstrate that whereas the R84C form has reduced activity, the L190R and A210P proteins are inactive. LHX4 mutations are a relatively rare cause of combined pituitary hormone deficiency. This report extends the range of phenotypes associated with LHX4 gene mutations and describes three novel exonic mutations in the gene.

Four Novel Mutations of the LHX3 Gene Cause Combined Pituitary Hormone Deficiencies with or without Limited Neck Rotation

The Lhx3 LIM-homeodomain transcription factor gene is required for development of the pituitary and motoneurons in mice. Human LHX3 gene mutations have been reported in five subjects with a phenotype consisting of GH, prolactin, TSH, LH, and FSH deficiency; abnormal pituitary morphology; and limited neck rotation. The objective of the study was to determine the frequency and nature of LHX3 mutations in patients with isolated GH deficiency or combined pituitary hormone deficiency (CPHD) and characterize the molecular consequences of mutations. The LHX3 sequence was determined. The biochemical properties of aberrant LHX3 proteins resulting from observed mutations were characterized using reporter gene and DNA binding experiments. The study included 366 patients with isolated GH deficiency or CPHD. In seven patients with CPHD from four consanguineous pedigrees, four novel, recessive mutations were identified: a deletion of the entire gene (del/del), mutations causing truncated proteins (E173ter, W224ter), and a mutation causing a substitution in the homeodomain (A210V). The mutations were associated with diminished DNA binding and pituitary gene activation, consistent with observed hormone deficiencies. Whereas subjects with del/del, E173ter, and A210V mutations had limited neck rotation, patients with the W224ter mutation did not. LHX3 mutations are a rare cause of CPHD involving deficiencies for GH, prolactin, TSH, and LH/FSH in all patients. Whereas most patients have a severe hormone deficiency manifesting after birth, milder forms can be observed, and limited neck rotation is not a universal feature of patients with LHX3 mutations. This study extends the known molecular defects and range of phenotypes found in LHX3-associated diseases.

Time‐Specific Effects of Perinatal Glucocorticoid Treatment on Anterior Pituitary Morphology, Annexin 1 Expression and Adrenocorticotrophic Hormone Secretion in the Adult Female Rat

Perinatal glucocorticoid (GC) treatment is increasingly associated with long-term disturbances in hypothalamo-pituitary-adrenocortical function. In the male rat, such treatment induces profound molecular, morphological and functional changes in the anterior pituitary gland at adulthood. To determine whether these effects are sex-specific, we have examined the effects of perinatal dexamethasone treatment on the female pituitary gland, focusing on (i) the integrity of the annexin 1 (ANXA1) dependent regulatory effects of GCs on adrenocorticotrophic hormone (ACTH) release and (ii) corticotroph and folliculo-stellate (FS) cell morphology. Dexamethasone was given to pregnant (gestational days 16-19) or lactating (days 1-7 post partum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the female offspring was examined ex vivo at adulthood (60-90 days). Both treatment regimes reduced the intracellular and cell surface ANXA1 expression, as determined by western blot analysis and quantitative immunogold electron microscopic histochemistry. In addition, they compromised the ability of dexamethasone to suppress the evoked release of ACTH from the excised tissue in vitro, a process which requires the translocation of ANXA1 from the cytoplasm to the cell surface of FS cells. Although neither treatment regime affected the number of FS cells or corticotrophs, both altered the subcellular morphology of these cells. Thus, prenatal dexamethasone treatment increased while neonatal treatment decreased FS cell size and cytoplasmic area. By contrast, corticotroph size was unaffected by either treatment, as also was the size of the secretory granules. Corticotroph granule density and margination were, however, increased markedly by the prenatal treatment, while the neonatal treatment had no effect on granule density but decreased granule margination. Thus, perinatal dexamethasone treatment exerts long-term effects on the female pituitary gland, altering gene expression, cell morphology and the ANXA1-dependent GC regulation of ACTH secretion. The changes are similar but not identical to those reported in the male.

Hypothalamic-pituitary magnetic resonance imaging in growth hormone deficiency

The accurate analysis of the hypothalamic–pituitary area is essential in the diagnosis of endocrine-related diseases. High-quality magnetic resonance imaging represents the examination modality of choice in the evaluation of hypothalamic–pituitary morphology. Indeed, the advent of molecular biology and neuroimaging techniques has led to significant progress in the understanding of the pathogenesis of disorders affecting the pituitary gland, specifically by demonstrating a clear phenotype–genotype relationship. Animal studies, along with the correlation of a particular genetic profile to certain endocrine and magnetic resonance imaging phenotypes in humans, have yielded great insights into pituitary development. Today, there is convincing evidence to support the hypothesis that marked magnetic resonance imaging differences in pituitary morphology indicate a variety of disorders that affect anterior pituitary gland organogenesis and function with a variety of diverse prognoses.

Perinatal Glucocorticoid Treatment Produces Molecular, Functional, and Morphological Changes in the Anterior Pituitary Gland of the Adult Male Rat

Stress or glucocorticoid (GC) treatment in perinatal life can induce long-term changes in the sensitivity of the hypothalamo-pituitary-adrenocortical axis to the feedback actions of GCs and, hence, in GC secretion. These changes have been ascribed largely to changes in the sensitivity of the limbic system, and possibly the hypothalamus, to GCs. Surprisingly, the possibility that early life stress/GC treatment may also exert irreversible effects at the pituitary level has scarcely been addressed. Accordingly, we have examined the effects of pre- and neonatal dexamethasone treatment on the adult male pituitary gland, focusing on the following: 1) the integrity of the acute annexin 1 (ANXA1)-dependent inhibitory actions of GCs on ACTH secretion, a process requiring ANXA1 release from folliculostellate (FS) cells; and 2) the morphology of FS cells and corticotrophs. Dexamethasone was given to pregnant (d 16-19) or lactating (d 1-7 postpartum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the offspring was examined ex vivo at d 90. Both treatment regimens reduced ANXA1 expression, as assessed by Western blotting and quantitative immunogold labeling. In particular, the amount of ANXA1 located on the outer surface of the FS cells was reduced. By contrast, IL-6 expression was increased, particularly by the prenatal treatment. Pituitary tissue from untreated control rats responded to dexamethasone with an increase in cell surface ANXA1 and a reduction in forskolin-induced ACTH release. In contrast, pituitary tissue from rats treated prenatally or neonatally with dexamethasone was unresponsive to the steroid, although, like control tissue, it responded readily to ANXA1, which readily inhibited forskolin-driven ACTH release. Prenatal dexamethasone treatment reduced the size but not the number of FS cells. It also caused a marked reduction in corticotroph number and impaired granule margination without affecting other aspects of corticotroph morphology. Similar but less marked effects on pituitary cell morphology and number were evident in tissue from neonatally treated rats. Our study shows that, when administered by a noninvasive process, perinatal GC treatment exerts profound effects on the adult pituitary gland, impairing the ANXA1-dependent GC regulation of ACTH release and altering the cell profile and morphology.

Correlation between the Pituitary Size and Function in Patients with Asthenia

To explore the relationship between pituitary morphology and function, we performed mid-sagittal MRI and endocrinological evaluation in 38 patients with asthenia. Six patients were diagnosed as having complete empty sella (ES) and 16 patients partial empty sella (PES). BMI, blood pressure, serum Na, ACTH, cortisol, TSH and T(4) were lower in ES group and PES group than in the group with normal pituitary size. Age in the patients with ES was oldest. Multiple regression analysis revealed that serum cortisol level was independently correlated with the size of the pituitary (beta = 0.586, p = 0.0069). Other variables, including age, BMI, blood pressure, serum Na, ACTH, TSH and T(4), were not correlated with the pituitary size when multivariate analysis was employed. In conclusion, there is a close relationship between the reduction of size of pituitary gland and the degree of adrenocortical dysfunction in asthenic patients. It is suggested that the pituitary-adrenal axis is especially vulnerable in empty sella syndrome, and therefore, meticulous evaluation of the hypophysial adrenal axis is recommended in subjects with reduced pituitary size even in elderly population.

Magnetic resonance imaging of the hypothalamus-pituitary unit in childrensuspected of hypopituitarism: who, how and when toinvestigate.

The magnetic resonance (MR) identification of pituitary hyperintensity in the posterior part of the sella has been the most striking recent finding contributing to the diagnosis of "idiopathic" and permanent GH deficiency (GHD). Moreover, advancements in DNA technology have shed new light on the study of the genetic causes of hypopituitarism. Abnormalities in two genes, the GH-N encoding the GH and the GHRH receptor (GHRH-R), have been identified, while mutations in five other gene-encoding transcription factors such as Pit-1, Prop-1, Hesx-1, Lhx-3 and Lhx-4 involved in anterior pituitary development, have also been described. MR imaging shows marked differences in pituitary morphology indicating different GHD etiologies and different prognoses. Ectopic posterior pituitary is a specific marker of permanent GHD. These patients do not have Pit-1, Prop-1, or Lhx-3 mutations and should be carefully monitored for evolving pituitary hormone defects, though they do not require GH re-evaluation in adulthood; selected cases may have Hesx-1 or Lhx-4 mutations. MR evidence of normal or small anterior pituitary gland, enlarged empty sella, pituitary hyperplasia and/or intrasellar or suprasellar mass when associated with combined pituitary hormone deficiency call for molecular analysis of Pit-1, Prop-1, Hesx-1, or Lhx-3. Limitation of neck rotation and Chiari-I malformation may suggest Lhx-3 or Lhx-4 mutations (exceedingly rare). In "idiopathic" isolated GHD, evidence of normal anterior or small anterior pituitary size with normal location of posterior pituitary and normal connection between the hypothalamus and pituitary gland is suggestive of "transitory" or false positive GHD; patients with such characteristics should be re-evaluated well before reaching adult height. In selected cases, anterior pituitary height that is 2 SD below age-adjusted normal pituitary height could be suggestive of GHRH-R gene defect; it is worth pointing out that normal pituitary MR together with severe GHD has been observed, though rarely, in subjects with a genetic origin of GHD.

Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe.

Pituitary morphology in patients with Prop1 gene mutations varies. Most patients demonstrate a normal or small pituitary gland. Occasionally, pituitary enlargement of undetermined origin has also been detected. In the present study we use long-term magnetic resonance imaging findings to characterize the morphological abnormalities of the pituitary gland in 15 patients (aged 2.5-45 yr) with combined pituitary hormone deficiency caused by Prop1 gene mutations (GA296del/GA296del in seven, GA296del/A150del in two, A150del/A150del in five, and GA296del/R73H in one patient) and attempt to uncover the origin and nature of the pituitary enlargement. Small pituitary gland was detected in seven patients (25.2 +/- 14.4 yr of age), normal pituitary size in three patients (10.2 +/- 5.8 yr of age), and pituitary enlargement in five patients (6.5 +/- 2.7 yr of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in three patients. Our data indicate that although a small pituitary gland is usually observed in older subjects, a significant number of young patients with Prop1 gene mutations demonstrate pituitary enlargement with subsequent regression. The distinct magnetic resonance imaging characteristics of the pituitary enlargement in our patients in conjunction with pertinent data from Prop1-deficient mice suggest that the mass causing the pituitary enlargement most likely originates from the intermediate lobe.

Idiopathic central diabetes insipidus is associated with abnormal blood supply to the posterior pituitary gland caused by vascular impairment of the inferior hypophyseal artery system.

Central diabetes insipidus (CDI) has been linked to vascular central nervous system damage, although the pathophysiology of the mechanism has never been perfectly understood. Indeed, the vascular system of human pituitary gland has rarely been the subject of rigorous investigation except at postmortem. Recently, studies of pituitary gland blood supply have been carried out by means of a time evaluation of pituitary gland enhancement with noninvasive dynamic magnetic resonance (MR) imaging after contrast medium injection. In the present study, we decided to investigate the status of posterior pituitary blood supply by evaluating vascular pituitary patterns in a group of 19 patients with idiopathic CDI in whom previous standard MR imaging had failed to identify causal specific lesions. The control group was composed of 55 subjects with a median age of 12 yr (range, 4.2-17 yr) who had idiopathic isolated GH deficiency and normal pituitary morphology and 15 young adults (18-25 yr) who had normal pituitary gland and no endocrine dysfunction. Nineteen patients (12 females and seven males), ranging in age at the time of diagnosis of CDI from 0.5-14.9 yr (median, 5 yr), were examined with dynamic MR imaging between 1990 and 1997 at a median age of 14.1 yr (range, 5.0-26.3 yr). CDI was diagnosed according to clinical findings of polyuria and polydipsia, water deprivation test, and desmopressin acetate therapeutic trial. All of the patients had permanent CDI and were being treated with satisfactory results with desmopressin, two to three times daily, either intranasally or orally. The previous MR imaging findings of the 19 CDI patients had shown the absence of posterior pituitary hyperintensity, normal pituitary stalk, and normal anterior pituitary size. Enhancement of the straight sinus, representing a temporal reference point and occurring in normal subjects simultaneously to that of the posterior pituitary gland, was observed in all subjects after iv gadopentetate dimeglumine administration, with no substantial differences between patients and controls. However, the enhancement of the posterior pituitary lobe occurred simultaneously with the enhancement of the straight sinus in all of the controls but in only 14 of the 19 patients with CDI. In the remaining five patients, the enhancement of the straight sinus was not associated with the expected contrast enhancement of the posterior pituitary gland, suggesting abnormal blood supply to the posterior pituitary lobe. This is in keeping with vascular impairment of the inferior hypophyseal artery system and suggests that abnormal blood supply to the posterior pituitary gland is associated with what, until now, has been considered idiopathic CDI.

Magnetic resonance imaging study of pituitary morphology in subjects homozygous and heterozygous for a null mutation of the GHRH receptor gene

Somatotrophs represent the majority of cells in the anterior pituitary, and their numeric reduction can cause anterior pituitary hypoplasia (APH). Small numbers of patients with familial isolated GH deficiency (IGHD) due to bi-allelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) have been reported to have APH. We tested if APH was present in a large cohort of patients homozygous and heterozygous for a GHRHR mutation. We studied pituitary morphology in adult and pediatric age subjects (8 years of age and older) belonging to a large extended Brazilian kindred with a high prevalence of IGHD due to a null GHRHR mutation. We performed brain magnetic resonance imaging (MRI) in 38 subjects, divided into four groups: group I: normal adults (five males, four females, age 38+/-11.7 years); group II: heterozygous adults (six males, seven females, age 42.23+/-8.8 years); group III: homozygous GH-naive affected adults (three males, five females, age 41.4+/-15.0 years); group IV: homozygous affected children (three males, five females, age 11.9+/-2.5 years). Results are expressed as means+/-s.d. Pituitary height (mm) was not different between groups II and I (4.61+/-1.55 and 4.41+/-0.62 respectively), but it was significantly reduced in groups III (2.67+/-0.87, P<0.001) and IV (2.87+/-0.79, P<0.001) compared with group I. Pituitary volume (mm(3)) was normal in group II (417.12+/-140.86), but it was significantly reduced in groups III and IV (124.06+/-64.27 and 155.68+/-39.79 respectively vs 414.56+/-71.57; both P<0.001). The volume ratio (calculated by multiplying the pituitary volume by 1000 and dividing it by cranial volume) was significantly lower in the affected subjects (groups III and IV) (0.06+/-0.02) than in unaffected (groups I and II) (0.15+/-0.04; P<0.0001), demonstrating that APH is not due to reduction of cranial volume. APH is present from childhood in patients homozygous for an inactivating GHRHR mutation, but it does not occur in heterozygous subjects. In our cohort, the presence of normal anterior pituitary size by MRI rules out homozygosity for a GHRHR mutation in subjects who are 8 years of age or older.

Isolated GH deficiency (IGHD) type II: imaging of the pituitary gland by magnetic resonance reveals characteristic differences in comparison with severe IGHD of unknown origin.

To determine the specific morphology of the pituitary gland in children with severe isolated GH deficiency due to GH-1 gene mutations (IGHD type II). The pituitary gland morphology in magnetic resonance imaging (MRI) of children with IGHD type II was analyzed and compared with the findings in a group of children with comparably severe IGHD of unknown origin. In addition, the birth histories of both groups were studied. Thirteen children with IGHD type II were diagnosed in seven European children's hospitals and they carried a corresponding GH-1 gene mutation. For comparison, we selected from a group of 66 MRI-studied GH-insufficient subjects diagnosed in our clinic, all children with severe IGHD (all GH peaks <4 microg/l) who had no GH-1 gene mutation, no first-grade relative with IGHD and no septo-optic dysplasia. Sagittal and coronal images of the brain were analyzed for the presence of any malformation of the pituitary gland and the intracranium. The height of each adenohypophysis was measured in a strict midline sagittal image for quantification of the gland's size. In addition, patients' files were reviewed for birth trauma or breech delivery. Normal MRI morphology of the pituitary gland was observed in all patients of the familial IGHD type II group (P<0.003) in which, however, five of thirteen patients (38%) exhibited a mild hypoplasia of their gland (mean sagittal adenohypophysial height -1.0+/-0.03 SD score (SDS)). In contrast, the pituitary gland in the idiopathic group showed a definitive malformation with hypoplasia of pituitary stalk and adenohypophysis in all cases, while ectopia of the neurohypophysis was present in nine of the ten cases. The adenohypophysis was significantly smaller in the idiopathic group (mean sagittal adenohypophysial height -3.2+/-0.3 SDS) (P<0.0001). All thirteen birth histories in the familial group (IGHD type II) were unremarkable while, in the idiopathic group, three of eight available birth histories recorded a breech delivery or traumatic birth (37.5%) (P<0.05). This study shows for the first time that MRI pituitary morphology may correlate with the etiology of severe IGHD: normal morphology suggests the presence of GH-1 gene mutations, while severe hypoplasia with malformation have other causes which might include so far unknown genetic defects as well as traumatic insults.

Pituitary morphology in the GH deficiency for mutation in the growth hormone-releasing hormone receptor gene

Pituitary morphology in the GH deficiency for mutation in the growth hormone-releasing hormone receptor gene

The tissue-specific transcription factor Pit-1 in the Antarctic notothenioid fish, Trematomus bernacchii

We have investigated the expression of the tissue-specific transcription factor Pit-1 and the distribution of some adenohypophyseal hormones belonging to the GH/PRL and POMC families in the pituitary of Trematomus bernacchii (Perciformes, Notothenioidei), by immunocytochemistry. Pit-1 is a member of the POU protein family, and it is responsible for GH, PRL and TSH cell commitment, differentiation and gene expression in mouse. Our results show coexistence of Pit-1, SL, GH and PRL in the pituitary of T. bernacchii. Cells containing SL, PRL and GH-like substances are widely distributed in the pituitary and coexist with Pit-1-like proteins. Moreover, SL is not expressed in the pars intermedia as demonstrated in other teleosts, and the peptides related to the proopiomelanocortin family are not colocalized with Pit-1, SL, GH and PRL. A few TSH cells are scattered throughout the pituitary and are not colocalized with Pit-1, SL, GH and PRL cells. We conclude that the pituitary gross morphology has peculiar characteristics and Pit-1 could be involved in the regulation of the GH/PRL/SL cell commitment, differentiation and gene expression in the pituitary of this Antarctic fish.

Characterisation of the pituitary gonadotrophs of FSH‐receptor knockout mice

To investigate further brain‐pituitary‐gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted (FSHRKO). FSHRKO females but not males are infertile. Compared with control animals, serum concentrations of LH and FSH and pituitary content of FSH are significantly increased in female FSHRKO (Abel et al. Endocrinology141, 2000). The aim of the present study was to correlate these physiological differences in gonadotroph function of 8‐week‐old‐female normal and FSHRKO mice with a structural analysis of their gonadotrophs. Gonadotrophs were identified by LH‐immunogold labeling for electron microscopy and gonadotroph frequency estimated from 1 (m sections immunolabelled for LH. In FSHRKO the frequency, cell and nuclear profile areas of gonadotrophs did not differ significantly from that in normal mice. Surprisingly the endoplasmic reticulum appeared normal and undilated despite the lack of oestradiol feedback in the KO animals. LH‐immunoreactive cells in female FSHRKO had significantly (P &lt; 0.05) larger secretory granules 176(7 nm) diameter, mean(SEM) compared to normal mice 139(7 nm) but there was no significant difference in the granule area/cytoplasmic area. The subpopulation of granules in which an electron‐dense core was present in a more electron‐lucent ‘halo’ was absent in FSHRKO gonadotrophs. The increased pituitary FSH stores in FSHRKO mice therefore appear to be represented by the formation of larger secretory granules in which the packaging of hormone is less dense. Interestingly, despite being infertile and lacking biologically active estrogen, the alterations in FSHRKO pituitary morphology are relatively subtle compared to normal mice.

MR imaging of pituitary morphology in idiopathic intracranial hypertension.

The aim of this study was to investigate the morphologic changes of the pituitary gland in patients with the clinical diagnosis of idiopathic intracranial hypertension (IIH). Qualitative and quantitative analyses of pituitary morphology were performed in normal subjects (n = 23), patients with the clinical diagnosis of IIH (n = 40), and patients with acute increased intracranial pressure (AICP; n = 37) caused by acute head trauma. The loss of pituitary height (concavity) on the sagittal T1-weighted image was classified into five categories: I = normal, II = superior concavity that was mild (<(1/3) the height of the sella), III = moderate (between (1/3) and (2/3) concavity of height of sella), IV = severe (>(2/3) concavity of height of sella), and V = empty sella. The area ratio of pituitary gland to sella turcica measured in the midsagittal plane was quantified. Clinical records were retrospectively reviewed to correlate with magnetic resonance (MR) findings. Using moderate concavity (>(1/3)) as the minimum criterion for abnormality, IIH patients had an 85% incidence of morphologic changes with 80% sensitivity and 92% specificity. Empty sella (almost complete concavity of the sella) was found in only 2.5% of patients with IIH. Quantitative analysis of the pituitary gland/sella turcica area ratio showed a significant decrease in patients with IIH (P < 0.0001) but no significant difference between the normal subjects and AICP patients. A posterior deviation of the pituitary stalk was seen in 43% of patients. No enlargement of the ventricles or sulcal effacement was seen in IIH patients. Routine brain MR examination of patients with IIH frequently shows morphologic changes of the pituitary gland ranging from various degrees of concavity to (rarely) the extreme case of an empty sella. The etiology is unknown and may be related to the severity and duration of elevated CSF pressure. Such findings may be useful to facilitate the diagnosis of IIH, particularly in patients with equivocal clinical findings or when IIH is not suspected. J. Magn. Reson. Imaging 2000;12:808-813.

Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene.

Pituitary is influenced by circulating and locally produced insulin-like growth factor I (IGF-I). To further elucidate the role of pituitary IGF-I, we compared pituitary morphology of homozygous (IgfI-/-), heterozygous (IgfI+/+), and wild-type (IgfI+/+) fetal and adult mice using light microscopy, immunocytochemistry, in situ hybridization and electron microscopy. In pituitaries of Igf1-/- and Igf1+/- fetal mice (day 18.5) GH RNA signal was decreased. In Igf1-/- adult females, GH cells were significantly diminished in size; GH RNA signal was stronger in Igf1-/- mice compared with IgfI+/+ mice, and the somatotrophs had ultrastructural features of stimulation. The number of PRL cells and PRL hybridization signal were significantly decreased, however plasma PRL levels were elevated in both genders. No changes in other cell types in Igf1-/- mice, and no alterations in Igf1+/- mice were evident. IGF-I treatment for 2 weeks of Igf1-/- mice increased significantly body weights, decreased GH hybridization signal, and had no effect on PRL cells, or PRL plasma levels, whereas in IgfI+/+ mice, PRL RNA signal and PRL plasma levels were markedly increased. In conclusion, IGF-I plays no role in differentiation of pituitary cells, affects the size of somatotrophs in females, and is a stimulator of lactotrophs in both genders.